SUPRAMAXIMAL SECRETAGOGUE STIMULATION ENHANCES HEAT-SHOCK PROTEIN EXPRESSION IN THE RAT PANCREAS

Heat shock or stress proteins (HSPs) are synthesized by various cell t ypes in response to different metabolic insults (e.g., hyperthermia). Although the function of HSPs is not fully understood, they are believ ed to be an evolutionary conserved intracellular defense mechanism. In an attempt to characterize the autoprotective potential of pancreatic acinar cells, we investigated the regulation of HSPs of the 70-kD fam ily and the small HSP ubiquitin in vitro and in vivo during supramaxim al cerulein stimulation. Infusion of the secretagogue cerulein induces a mild edematous form of pancreatitis in vivo and is characterized by a marked disturbance of the intracellular transport and segregation o f enzymes. Synthesis of HSP70 mRNA is upregulated in isolated pancreat ic lobules by either cerulein (100 nM) or hyperthermia (42 degrees C f or 60 min). In contrast, expression of ubiquitin mRNA was not altered by either secretagogue treatment or hyperthermia. This heat shock-like response of pancreatic acinar cells could be reproduced in vivo: Panc reatitis was induced in male Wistar rats by intravenous infusion of su pramaximal doses of cerulein (10 mu g/kg/h). Analysis of mRNA expressi on revealed a significant upregulation of HSP70 RNA during supramaxima l secretagogue stimulation. mRNA levels encoding for ubiquitin remaine d unchanged. Western blot analysis demonstrated that the transcription al upregulation of HSP70 in vivo was reflected on the protein level. T his study demonstrates that the marked intracellular disturbance obser ved in secretagogue-induced pancreatitis is associated with enhanced e xpression and synthesis of a major stress protein. Given the autoprote ctive potential of HSPs, this upregulation may indicate a self-defense mechanism of pancreatic acinar cells in experimental pancreatitis.